The importance of angiogenesis in a variety of disease processes, in inflammatory reactions, during the course of graft-versus-host reactions, in delayed hypersensitivity reactions, and as an accompaniment of tumor growth is well recognized. Angiogenesis, moreover, has particular relevance to several ocular diseases and probably plays a major role in the pathogenesis of diabetic retinopathy. The purpose of the proposed research is to exploit more fully the newly developed methodology for obtaining neovascular reactions following implantation of tumors or allogeneic lymphoid cells into the mouse cornea. Specifically, we hope to define more precisely the nature of the induced vascular responses, to characterize the types of cells that evoke these responses, to isolate and characterize some of the chemical factors that may lead to neovascular reactions, and to analyze the effects of various pharmacologic and immunologic agents on angiogenesis. In these studies we plan to take advantage of the extensive background information available for the mouse and to utilize mutant mouse strains in our experimental approach to angiogenesis. It is hoped that from these studies will come a better understanding of the factors leading to angiogenesis and that this understanding, in turn, may be useful in developing methods for controlling abnormal neovascular responses.